Abstract
Considerable clinical successes have been achieved in cancer treatment since the introduction of targeted therapies. However, almost inevitably tumors develop therapy resistance, which limits durable clinical responses. Tumors are often heterogeneous, and as a result, therapy‐resistant cells are present even before the start of treatment. Resistance is commonly mediated via genetic changes. However, in this issue of EMBO Molecular Medicine, Smith et al (2017) report that phenotypic heterogeneity can contribute to resistance as well.